The introduction of clozapine provided an option for schizophrenic patients refractory to all other treatments. However, only 30%-60% of schizophrenic patients refractory to standard treatments will respond to treatment with clozapine. This lack of complete success has prompted the frequent use of various clozapine augmenting strategies with agents such as additional antipsychotics, benzodiazepines, antidepressants, and mood stabilizers, despite a lack of controlled trials demonstrating the clinical usefulness or safety of such strategies. To date, only a single controlled trial has demonstrated the effectiveness of one such strategy, a combination of sulpiride and clozapine, which is an option not available to U.S. practitioners. An open label trial of an alternative strategy involving pimozide augmentation of clozapine in schizophrenic patients non- or partially responsive to clozapine monotherapy demonstrated this treatment to be very effective as evidenced by a dramatic reduction in serial ratings of schizophrenic symptoms and a reduction in hospital stays. Pimozide's unique pharmacological and clinical properties may contribute to the enhanced effectiveness of clozapine when pimozide is added. Therefore, this project proposes to enroll 64 clozapine-refractory schizophrenic and schizoaffective patients into a 16 week double blind, placebo controlled trial evaluating the comparative efficacy of the pimozide-clozapine combination to clozapine combination treatment involving placebo in treating symptoms of schizophrenia. This study will provide sorely needed controlled data on the efficacy and safety of a clozapine combination treatment strategy involving adjunctive antipsychotic agents. [unreadable] [unreadable]